Cardiovascular drugs in children: Angiotensin-converting enzyme inhibitors

Summary Angiotensin-converting enzyme inhibitors are potent vasodilators acting by inhibition of production of the vasoconstrictor angiotensin II. In adults, they are used for treatment of systemic hypertension and congestive heart failure and investigated for treatment of primary pulmonary hypertension.In infants and children, saralasin and captopril were found to be useful in treatment of systemic arterial hypertension, especially when associated with high plasma renin activity. Captopril has failed in the treatment of congestive heart failure associated with complex congenital heart diseases and in most cases of primary pulmonary hypertension. It has a clear beneficial effect in coarctation of the aorta and may have such an effect in endomyocardial diseases and ventricular septal defect.In adults, serious side effects have limited the use of captopril. New converting enzyme inhibitors, devoid of a sulfhydryl group, are expected to have a better safety profile.     

1型糖尿病青少年患者血糖控制和糖尿病微血管并发症

为了解1型糖尿病青少年患者的血糖控制情况、糖尿病微血管并发症的发生率及其危险因素 ,调查病程5年以上的1型糖尿病患者76例 ,平均年龄17.2±3.9岁 ,平均病程9.0±3.4年 ,检测餐后2小时血糖、糖化血红蛋白 (HbA1C)、尿微量白蛋白 ,眼底荧光造影等。结果显示 ,HbA1C 平均水平为 (9.7±1.7) % ;糖尿病肾病发生率为9.2% ,微量白蛋白尿 (UAER :20～200μg/min)和大量蛋白尿 (UAER>200μg/min)分别占7.9 %和1.3 %;糖尿病视网膜病变发生率为23.7% ,非增殖型16例占21.1% ,增殖型2例占2.6 % ,其中3例合并白内障。提示目前1型糖尿病青少年患者的血糖控制不理想 ,仅有18.4 %的患者HbA1C <8 % ;长病程、女性、血糖控制差是1型糖尿病青少年发生糖尿病视网膜病变、糖尿病肾病的危险因素     

Evaluation of sensorimotor polyneuropathy in children and adolescents with type I diabetes: associations with microalbuminuria and retinopathy

Abstract: To investigate diabetic polyneuropathy, we measured peroneal motor conduction velocity, sural sensory nerve conduction velocity and vibratory sense threshold (biothesiometry) in 28 children and adolescents with insulin-dependent diabetes (type 1), and in 28 age- and sex-matched, normal controls. Age varied from 8 to 19 yr (mean ± SD = 13.04 ± 2.61); age at the onset of diabetes from 9 months to 12 yr (4.53 ± 2.42 yr); and the duration of diabetes from 5 to 16 yr (8.48 ± 2.98). Eight patients (28%) fulfilled the minimal criteria for the diagnosis of polyneuropathy. Four of these patients showed symptoms while three had clinical signs of neuropathy. Eight patients had abnormal, sural sensory nerve conduction velocities. The presence of polyneuropathy did not correlate with the duration of diabetes or degree of metabolic control of diabetes. The prevalence of microvascular complications (microalbuminuria and retinopathy) was 32%. The presence of microvascular complications did not correlate with metabolic control but did with the duration of diabetes. The relationship between polyneuropathy and microvascular complications was 34%.     

血管紧张素转换酶2对儿童2019冠状病毒病的作用研究进展

随着严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在全球的肆虐,儿童感染者人数也越来越多。血管紧张素转换酶2（ACE2）是SARS-CoV-2感染人体的结合位点之一,可以与病毒尖峰蛋白结合,使得跨膜丝氨酸蛋白酶（TMPRSS2）启动S蛋白触发感染,引起白细胞介素-1、干扰素-γ、肿瘤坏死因子等多种炎性因子的产生。与成人相比,儿童的ACE2及TMPRSS2的表达水平较低,推测儿童症状较成人轻,发病人数较成人少均与此有关。该综述对SARS-CoV-2感染过程中ACE2的作用研究进展进行总结,有助于了解SARS-CoV-2的致病机制,为更好地开发药物及疫苗,防治儿童2019冠状病毒病提供参考。     

Low risk of overt nephropathy after 24 yr of childhood-onset type 1 diabetes mellitus (T1DM) in Norway

AIM: To estimate the risk of diabetic nephropathy and associated risk factors in a nationwide cohort of childhood-onset type 1 diabetes mellitus (T1DM) and 19-30 yr of diabetes duration. METHODS: Patients diagnosed with childhood-onset T1DM (<15 yr) from 1973 through 1982, who previously (1989-1990) participated in a clinical examination to assess diabetic complications, were invited for a new examination in 2002-2003. Of 355 eligible patients, 299 participated (84.2%), and complete urine samples for evaluation of albuminuria were obtained from 295 patients, with a mean age of 33 yr (range 20.9-44.0) and mean diabetes duration of 24 yr (range 19.3-29.9). Persistent microalbuminuria and overt nephropathy [albumin excretion rate (AER) 15-200 microg/min and AER > 200 microg/min, respectively] in at least two out of three consecutive overnight urine samples were defined as diabetic nephropathy. RESULTS: Overt nephropathy was found in 7.8% [95% confidence interval (CI) 4.7-10.9] and persistent microalbuminuria in 14.9% (95% CI 10.8-19.0) of the subjects. Hemoglobin A1c (HbA1c) (p = 0.001), systolic blood pressure (BP) (p = 0.002), total cholesterol (p = 0.019), and C-reactive protein (CRP) (p = 0.019) were associated with diabetic nephropathy. Significant predictors in 1989-1990 for the development of diabetic nephropathy in 2002-2003 were HbA1c (p < 0.001), AER (p = 0.007), and cholesterol (p = 0.022). CONCLUSIONS: In a subgroup of patients diagnosed with childhood-onset T1DM in 1973-1982, 7.8% had overt nephropathy after 19-30 yr of diabetes duration, which is low compared with studies from other countries. HbA1c, systolic BP, total cholesterol, and CRP were each independently associated with diabetic nephropathy.     

Microvascular complications assessment in adolescents with 2- to 5-yr duration of type 1 diabetes from 1990 to 2006

Cho YH, Craig ME, Hing S, Gallego PH, Poon M, Chan A, Donaghue KC. Microvascular complications assessment in adolescents with 2‐ to 5‐yr duration of type 1 diabetes from 1990 to 2006. Objective: Microvascular complications occur in adolescents with type 1 diabetes, although guidelines vary as to when screening should commence and prevalence data for those with ≤5‐yr duration are limited. We therefore investigated trends in prevalence of early microvascular complications over 17 yr. Research design and methods: 819 adolescents (54% female) aged 11–17 yr with 2‐ to 5‐yr diabetes duration were assessed for complications at a tertiary pediatric diabetes clinic between 1990 and 2006. Early retinopathy was detected using seven‐field fundal photography, albumin excretion rate (AER) by timed overnight urine collections and peripheral nerve function by thermal/vibration threshold at the foot. Results were analyzed by age, time period of assessment, and duration. Results: Early retinopathy declined from 1990 to 2002 (16–7%, p < 0.01), then remained unchanged until 2006. Early elevation of AER (≥7.5 µg/min) and microalbuminuria (≥20 µg/min) did not change over time, whereas peripheral nerve abnormalities increased (14–28%, p < 0.01). Median hemoglobin A1c improved (8.7–8.2%, p < 0.01), in parallel with increased total daily insulin dose and injections per day (p < 0.01). Body mass index standard deviation score increased over time (0.55–0.79, p < 0.01). In multivariate logistic regression, early retinopathy was associated with earlier time period [odds ratio (OR) 0.68, confidence interval (CI) 0.55–0.85, p < 0.01] and older age (OR 1.19, CI 1.02–1.39, p = 0.03). AER ≥ 7.5 µg/min was associated with older age (1.19, 1.06–1.34, p < 0.01) and longer diabetes duration (OR 1.28, CI 1.02–1.62, p = 0.04) and height‐adjusted peripheral nerve abnormalities with later time period (OR 1.26, CI 1.05–1.50, p = 0.01). Conclusions: Early complications are not uncommon in adolescents with 2‐ to 5‐yr diabetes duration, despite more intensive management in recent years.     

Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

BACKGROUND: Insulin resistance is well recognized both in type 1 diabetes mellitus (T1DM) and in obesity. Studies concerning the relation between insulin resistance and overweight in T1DM have not yet been carried out. METHODS: Degree of overweight [standard deviation score-body mass index (SDS-BMI)] and daily insulin doses per weight (ID/kg), per body surface (ID/m2), and per ideal body weight (ID/IW) were recorded in 4124 children aged between 5 and 20 yr with a duration of T1DM of 4-5 yr and an adequate metabolic control [hemoglobin A1c (HbA1c) <8.0%]. SDS-BMI was compared between insulin-resistant (ID/kg > or = 1.0) and insulin-sensitive (ID/kg <1.0) children. The ID/kg, ID/m2, and ID/IW were compared between obese (SDS-BMI >1.9) and non-obese children. Multivariate linear regression analysis was conducted for the dependent variables ID/kg, ID/m2, and ID/IW, including age, gender, SDS-BMI, and HbA1c as independent variables. RESULTS: The 882 insulin-resistant children did not differ significantly (p = 0.447) with respect to SDS-BMI (median +0.38) compared to the 3242 insulin-sensitive children (median SDS-BMI +0.42). The ID/kg was significantly (p = 0.031) lower in the obese children compared to the non-obese children (median 0.80 vs. 0.83), while ID/m2 (median 31.0 vs. 26.2) and ID/IW (median 1.17 vs. 0.85) were significantly (p < 0.001) increased in the obese children. In multivariate linear regression analysis, SDS-BMI was significantly (p < 0.001) associated with an increase in ID/m2 and ID/IW and a decrease in ID/kg. CONCLUSIONS: T1DM children with insulin resistance based on ID/kg are not more overweight than insulin-sensitive children with T1DM. ID/m2 and ID/IW seem to reflect a better tool than ID/kg to describe the influence of overweight on insulin resistance in T1DM.     

Carotid artery intima-media thickness and angiotensin-converting enzyme gene polymorphism in the offspring of parents with premature stroke

Aim: To determine some common cardiovascular risk factors, alterations in the measurements of intima-media thickness (IMT) and the distribution of the angiotensin-converting enzyme (ACE) polymorphism in children of parents with premature stroke, and to investigate the cardiovascular risk of these children and the potential need for some preventive measures.Methods: A family history of cardiovascular disease represents a cardiovascular risk factor in the offspring. This association has not yet been clearly determined for cerebrovascular accidents. New technology allows us to investigate the risk for cardiovascular disease at an early presymptomatic stage. We applied the measurement of IMT of carotid arteries by ultrasound imaging and the determination of the ACE insertion/deletion (I/D) polymorphism in blood to evaluate the predisposition for cerebrovascular disease in the offspring of patients with previous stroke. We investigated 58 subjects whose parents had experienced a cerebrovascular accident before the age of 45 y and compared them with a matched control group whose parents had not suffered a stroke. Results: The results of IMT at various sites of the carotid arteries and the genotype distribution of the ACE gene were not significantly different between the study group and the control group. In addition, no differences were found in the serum levels of lipid fractions or other biochemical variables.

Conclusion: We conclude that determination of the carotid IMT and of the ACE I/D polymorphism do not permit discrimination of the cardiovascular risk in children of parents with or without premature stroke.     

Bone turnover markers in children and adolescents with type 1 diabetes—A systematic review

Type 1 diabetes (T1D) is associated with impaired bone health and both osteocalcin (OCN) and procollagen type 1 amino terminal propetide (P1NP) (markers of bone formation) and C‐terminal cross‐linked telopeptide (CTX) (marker of bone resorption) are decreased in adult patients with T1D. We review the existing literature characterizing these bone turnover markers in children and adolescents with T1D and by meta‐analysis examine whether alterations in OCN, P1NP, and CTX are evident and if potential changes correlate to the metabolic control (hemoglobin A1c, HbA1c). Systematic searches at MEDLINE and EMBASE were conducted in January 2018 identifying all studies describing OCN, P1NP, or CTX in children and adolescents with T1D. A total of 26 studies were included, representing data from more than 1000 patients with T1D. Pooled analyses of standard mean difference and summary effects analysis were performed when sufficient data were available. Pooled analysis revealed mean OCN to be significantly lower in children and adolescents with T1D compared to healthy controls (standard mean difference: ?1.87, 95% confidence interval, CI: ?2.83; ?0.91) whereas both P1NP and CTX did not differ from the controls. Only data on OCN was sufficient to make pooled correlation analysis revealing a negative correlation between OCN and HbA1c (?0.31 95% CI: ?0.45; ?0.16). In conclusion, OCN is decreased in children and adolescents with T1D, whether CTX and P1NP are affected as well is unclear, due to very limited data available. New and large studies including OCN, P1NP, and CTX (preferably as z‐scores adjusting for age variability) is needed to further elucidate the status of bone turnover in children and adolescents with T1D.     

Treatment of hypertension and microalbuminuria in children and adolescents with type 1 diabetes mellitus

Abstract: Nephropathy is the main cause of morbidity and mortality in patients with type 1 diabetes and, in adults, persistent microalbuminuria is the best marker of the consequent risk for its development. In the pediatric population, puberty represents the most important risk factor for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. As many as 50% of subjects may revert to normoalbuminuria. Hypertension is a further risk factor and may accelerate the progression of micro- and macrovascular complications. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects – hence they represent the drug of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific, they may become the obvious treatment choice in the near future. There is no consensus as to who should be treated and when treatment with renoprotective drugs should begin in the pediatric population, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review some models and controversial aspects of this issue are presented and discussed.